Multicomponent Intervention for Overactive Bladder in Women

Key Points Question What is the efficacy of a multicomponent intervention with cognitive components in improving health-related quality of life (HRQOL) for women with moderate to severe overactive bladder (OAB)? Findings In this randomized clinical trial of 79 women, those who underwent four 30-minute weekly sessions of a multicomponent intervention had a significantly and clinically significant improvement in HRQOL scores compared with the waiting list control group. Meaning These findings provide evidence to support a multicomponent intervention with cognitive components as an effective treatment option for women with moderate to severe OAB by improving HRQOL.

provided for those who wish to use.
Control group: No additional treatment during the study period.If on medical treatment, participants will continue the baseline medical treatment only.CBT will be provided at the end of the study.If desired, CBT will be conducted online using a web conferencing application.

Outcomes
Primary outcome: -Health-related quality of life (HRQoL) total score of Overactive Bladder Questionnaire (OAB-q) (2) Secondary outcomes: -The other subscales of OAB-q (2) OAB was defined by the International Continence Society (ICS) in 2002 as a symptom syndrome in which urinary urgency is essential, usually accompanied by urinary frequency and nocturia, and urge incontinence is not essential (7).It is generally recognized as a disease concept consisting of symptoms such as urinary urgency, frequent urination, nocturia, and urge urinary incontinence.According to the guidelines for OAB, urinary urgency is a sudden, unbearable urge to urinate that is difficult to explain and differs from the normal urge to urinate (8).Urge urinary incontinence is defined as an involuntary leakage of urine at the same time as or immediately after the urge to urinate (8).

Prevalence of OAB
The epidemiology of OAB in Japan was reported in a large epidemiological survey in 2002 (9).In this epidemiological survey, 10,096 men and women aged 40 years or older were randomly sampled from 75 sites nationwide, and the prevalence of OAB in women was 10.8%, with a tendency to increase with age.The number is expected to increase further in the aging society.

Impact of OAB on quality of life
OAB is a chronic condition that does not cause death by itself.However, complete cure is difficult, and the more severe the symptoms, the more impaired the quality of life (QoL) is known to be (10).

Impact of OAB on Medical Economics
The total cost related to OAB in Japan, calculated based on the prevalence rate in a large-scale epidemiological survey in 2002, was 956.2 billion yen per year (11).The breakdown was 180.9 billion yen (19%) for the treatment of OAB (including 159.1 billion yen for drug treatment), 92.7 billion yen (6%) for the treatment of OAB comorbidities, 28.7 billion yen (3%) for urinary incontinence-related costs, and 684.6 billion yen (72%) for labor losses.Furthermore, with or without treatment, the cost was estimated at 112,000 yen per symptomatic patient.With the super-aging of the population, its impact on the healthcare economy is expected to increase.

Current status of OAB treatment
The 2015 revised guidelines for the treatment of OAB describe behavioral, pharmacologic, neuromodulation, and surgical therapies for the treatment of OAB.The most commonly used treatment for OAB is pharmacotherapy, especially anticholinergic drugs, the efficacy of which is well-established (8).However, there are many reports of side effects associated with systemic muscarinic receptor blockade, including dry mouth and constipation, and a systematic review reported that 43-83% of patients discontinue medication within one month (12).Recently, a large case-control study reported an association between anticholinergics and the development of dementia (odds ratio 1.11, 95% confidence interval 1.08-1.14)(13).Neuromodulation therapy and surgical treatment methods are invasive treatments, and the number of facilities that perform them is limited.Because of its safety, the guidelines of the American Urological Association list behavioral therapy as the first-line treatment (14).However, treatment programs are not well-established.Especially in Japan, it is not widely used because it has not been determined who, where, and how it should be conducted, and it is not reimbursed by medical costs.

Cognitive behavioral therapy (CBT)
CBT is a form of psychotherapy developed by Aaron T. Beck in 1963 from cognitive therapy for depression (16).Since then, it has been widely used for anxiety disorders such as panic disorder and obsessive-compulsive disorder, as well as other psychiatric disorders.The theory of CBT is based on the fact that cognition (the way one thinks and perceives things) affects emotions and behavior, which in turn manifest themselves as physical symptoms.External stress distorts cognition, which in turn affects emotions and behavior, causing physical symptoms, which in turn distort cognition further, creating a vicious cycle.This leads to disease.CBT corrects distorted cognition and behavior and cures symptoms.
CBT is characterized by:  Aiming to solve the problem in the here and now.
 The therapist and the research participant working together to set goals and determine a treatment plan (cooperative positivism).
 Both sessions and programs being structured.
 Treatment following a cognitive behavioral model.
In addition to psychiatric disorders, it has been reported to be effective for other non-psychiatric disorders such as chronic pain (17) and irritable bowel syndrome (18).OAB can also be addressed using the cognitive behavioral model (see figure below), and we believe that a CBT approach that includes the aforementioned behavioral therapy may also be effective.

About the pilot study
To evaluate the feasibility of CBT for drug-resistant OAB, a pilot study of 10 cases was conducted from April 2019 to October 2019 (approved by the Kyoto University Medical Ethics Committee, receipt number: C1423, approval date: January 16, 2019, "Conventional A Single-Group, Uncontrolled Intervention Study of the Feasibility and Efficacy of a Combined Behavioral Therapy and Psychological Intervention Program for Drug-Resistant Overactive Bladder").There was one participant who dropped out of the study due to an adverse event (AE), but it was not related to the study.Other participants completed the study without AEs.Although statistical tests were not performed, both primary and secondary outcomes improved before and after the intervention.Based on the results of the pilot study, we concluded that it was worthwhile to evaluate the efficacy of CBT for OAB and decided to design this study.

Thoughts
Remember going to toilet

Moods/ Feelings
Anxious worried

Rush into toilet
The purpose of this study is to establish CBT for OAB based on conventional behavioral therapies and to evaluate its efficacy in women with moderate to severe OAB in a randomized controlled trial.

Study design
Open-label, parallel-group, multicenter, 1:1 randomized controlled trial (1) Women between 20-80-year-old; (2) Participants not having undergone any OAB treatment for more than 6 weeks or participants taking pharmacotherapy lasting more than 6 weeks for OAB; (3) Participants diagnosed with OAB based on their OAB symptom score (OABSS)* (a total OABSS score ≥3, with an urgency score ≥2), with the total score being higher than It is a symptom score for OAB developed in Japan and used worldwide for diagnosis and severity assessment (1).A urinary urgency score (Question 3) of 2 or higher and a total score of 3 or higher are considered a diagnosis of OAB.Regarding severity, a total score of 5 or less is considered mild, a score of 6-11 moderate, and a score of 12 or more severe.

Selection of Study Participants
During recruitment (see 23), individuals interested in participating in this study will be asked to visit a research collaborating facility and undergo a general medical examination for OAB.The general examination for OAB aims to determine the diagnosis and severity of the condition through a questionnaire-based interview and ultrasound to rule out abnormalities around the bladder.Those who meet the inclusion and exclusion criteria will be provided with an explanation of the study, and those who give their consent will be included in the study.

Intervention CBT program used in this study
In addition to the conventional behavioral therapy that has been used for OAB (3,4), CBT techniques (1,2,5,6) known to be particularly effective for OAB will be employed.
(1) Participant education A general explanation of OAB and CBT will be provided, and short-and long-term goals for undergoing this treatment will be set.This will also foster a cooperative relationship between the participant and the treatment interventionist.
(2) Self-monitoring The participant will maintain a urinary diary (FVC) to monitor their current status independently.By continuing this practice not only during the treatment evaluation but also throughout the intervention period, the patient can observe the changes in their urinary status.This will help them identify and overcome their own challenges, and the visible improvement will enhance their self-efficacy.
(3) Lifestyle modifications Identify lifestyle habits that may be risk factors for OAB (excessive water intake, caffeine consumption, alcohol consumption) and establish strategies to improve them.(5) Exposure While the urge to urinate can be avoided by emptying the bladder frequently, the act of frequent urination actually promotes the urge to urinate, leading to a vicious cycle.
Exposure (endurance) to the uncomfortable situation (urge to urinate) is encouraged to increase tolerance to the urge (to extend the interval between urinations).A step-by-step schedule should be planned, and the urination interval should be gradually increased by consistently following the schedule.(3) a relapse prevention phase (1 session), totaling 4 sessions.As a basic rule, interventions will be conducted every week, but a maximum interval of three weeks will be allowed (an interval of more than three weeks will be considered a deviation from the intervention).If the patient is already on oral therapy, the CBT should be coordinated with the oral therapy.
Due to concerns about the risk of novel coronavirus transmission, the intervention will be conducted online using a web conferencing application for those who wish to participate.The web conferencing application chosen for this purpose is Zoom, a free web conferencing service provided by Zoom Video Communications, Inc. of the United States (https://zoom.us/).A reminder email containing the Zoom appointment details will be sent to the participants one day before the intervention.The intervention will be conducted using Zoom, following the same treatment intervention program as the in-person sessions.
Brief summary of CBT manual for drug-resistant OAB.

Therapist
The treatment therapist in this study shall be qualified as a specialists and supervisors certified by the Japanese Urological Association, with a minimum of 10 years of clinical experience.Additionally, participation in the CBT workshop, a training program conducted by the Ministry of Health, Labor, and Welfare, is mandatory.

Assurance of Quality of Intervention
To ensure the quality of interventions, a review committee comprising urologists, obstetricians/gynecologists, psychiatrists, clinical psychologists, and physical therapists was established, and a treatment manual was developed.The therapist will conduct interventions in accordance with this manual.A checklist is prepared for each session to verify the achievement of each item.

Review session 3 and homework Relapse prevention
Plan the future's goal and encourage to continue the techniques Total review 5.4.Treatment of the control group CBT will not be administered during the study period.If the patient is receiving a drug treatment, only the baseline treatment will be continued.CBT will be provided after the completion of the study.Online CBT using a web conferencing application will be conducted for those who wish to participate.

Data collection 6.1 Baseline characteristics
Age, height, weight, medical history, childbearing experience, menopause, highest education level completed, marital status, occupational history, and history of dysuria treatment will be assessed using a questionnaire at baseline.

Outcomes
Primary outcome: -Overactive Bladder Questionnaire (OAB-q) HRQoL total score (2) This is a QOL self-reported questionnaire specific to OAB.It consists of questions regarding the degree of distress and QOL due to symptoms.Week 13 (end of follow-up) is the primary assessment point.The HRQoL total score of the OAB-q is calculated on a 100-point scale as follows: Minimum Clinical Important Difference (MCID) is 10 points (20).-OAB-q subscales other than HRQoL total scores (2) The subscales other than the HRQoL total score are calculated as follows.A multi-item option to evaluate the general improvement score of symptoms using a 7-point Likert scale self-administered questionnaire, with 1 to 2 defined as improvement, and a binary variable of with improvement and without improvement.
-Patient Global Impression-Severity (PGI-S) (4) It is a multiple-choice instrument that evaluates the overall improvement score of symptoms using a 4-point Likert scale self-administered questionnaire. 1 to 2 is defined as improvement, and is evaluated with and without improvement as a binary variable.
-Hospital Anxiety and Depression Scale (HADS) (6) A 14-item self-administered questionnaire developed to assess anxiety and depression in participants with physical symptoms.Anxiety and depression are calculated by summing the scores from a point distribution table.Scores of 0-7 indicate no anxiety or depression, scores of 8-10 are suspicious diagnoses, and scores of 11 or higher are confirmed diagnoses.

-Frequency voiding chart (FVC)
The following information is entered in a self-administered form: waking time, sleeping time, time of urination, amount of urination per time, frequency of urination, and presence or absence of urinary incontinence with a sense of urgency.Of these, the average number of urination, urinary incontinence, and urinary urgency frequency per 24 hours will be used as the evaluation items.
-Patient Satisfaction A general improvement score of symptoms was used as a multiple choice to be evaluated using a self-administered questionnaire with a 5-point Likert scale. 1 to 2 is defined as satisfaction with treatment and is evaluated with a binary variable of satisfied or not satisfied.-Dropout rate The percentage of assigned participants who drop out during the study will be calculated.There will be two types of dropouts in this study: intervention discontinuation and evaluation discontinuation (see "9. Discontinuation Criteria" for details).

Measurement methods
OAB-q, OABSS, KHQ, GIS, EQ-5D-5L, HADS, FVC, and treatment compliance before the start of CBT, at Week 5 (after treatment ends), Week 9 (4 weeks after treatment ends), and Week 13 (at the end of follow-up) of the paper or online-based registration system (REDCap*) Patients will be asked to complete a self-administered questionnaire.Dropout rates and incidence of AEs will be confirmed by the therapist at each visit.Treatment feedback will be completed at the end of follow-up, either on paper or in a self-administered questionnaire in REDCap*.The same will be done for the study at all sites, and data will be collected online with security assured.
* REDCap is a data collection and management system developed by Vanderbilt University in the U.S. under the NIH Clinical Bridging Research Support Grant and distributed free of charge mainly to academia, and is used at 3090 facilities in 128 countries around the world.In Japan, Osaka City University provides the system; on April 1, 2017, the Department of Clinical Statistics, Graduate School of Medicine, Kyoto University contracted with Osaka City University to begin research use of the system.Under this contract, the data server is dedicated to Kyoto University, which is contracted by Osaka City University, and its management is entrusted to Osaka City University.The data server is equipped with complex security measures.Access to the server and system is restricted by user accounts and passwords issued to individuals, and all audit trails are recorded.
The schedule of this study.

Registration and random allocation 7.1. Enrollment procedure
Women aged 20-80 years who have been diagnosed with moderate to severe OAB at the time of their first visit or while attending a participating facility for the study will be screened through a general medical examination using a questionnaire and ultrasound.
After confirming that the participants meet the eligibility criteria and do not meet the exclusion criteria, an explanation of the study will be provided using the study's explanatory consent document.The potential participants will be informed that participation is voluntary, they can withdraw even after participation, and that non-participation will not be detrimental to their treatment.Once consent is obtained for the explanation, the document will be signed.After receiving consent, basic information and OABSS scores will be entered into REDCap (see 6.3), and the participant will be registered.Each enrolled participant will be assigned an enrollment number by the site, and the enrollment number assigned by REDCap will be used to manage the data of enrolled participants for the entire study.

Random allocation procedure
Random allocation will be made 1:1 to the intervention or control group by the minimization method based on the basic information registered in REDCap and the assignment factors from OABSS on the computer.Allocation will be done by registration in the UMIN INDICE cloud system* (registration number: C00073) and using the algorithm in the system.During the first week of the intervention, the results Follow-up Close-out of the allocation will be communicated simultaneously to the therapists and the participants via an Internet screen.The intervention group will be informed that the intervention will start on the day of allocation, while the control group will be informed that no intervention will be given during the treatment period, and that the intervention will be given after the completion of the study.
*UMIN INDICE Cloud System (https://www.umin.ac.jp/indice/cloud.html)This is a cloud system provided by UMIN that allows random assignment by the minimization method.If the difference between the two groups exceeds a certain level, the patients are assigned to the group with the lowest allocation.If the difference between the two groups is less than a certain level, random assignment is possible.Age is considered the most significant risk factor for OAB, and the understanding of CBT may differ according to age, and the effectiveness of the intervention may also differ.We believe that OAB severity strongly influences intervention effectiveness.
Intervention effectiveness may differ depending on whether CBT alone or in combination with oral medication is used.The backgrounds of the participants are expected to differ between facilities.For these reasons, age, OAB severity, presence of medical treatment, and facility were used as allocation factors.

Random allocation by minimization method
Each allocation factor will be summed, and if the difference between the two groups is greater than 2, the patient will be assigned to the allocation group with fewer allocation factors.If the difference between the two groups is less than 2, random assignment will be done to the randomly assigned group.The allocation factors will be entered into the UMIN INDICE cloud system in front of the therapist/participant or via online screen sharing during Week 1, and the allocation will be done on the spot.

Masking
Due to the nature of the intervention, this study cannot be masked to the therapist/participant.Statistical analysts will not be able to review the results until the end of the study.In addition, REDCap keeps a complete history, so the history can be traced for any evidence of confirmation of the results.

Discontinuation criteria
There will be two types of discontinuations from the study: intervention discontinuation and evaluation discontinuation.

Deviation from protocol treatment
Any of the following will be considered a deviation from the protocol treatment.In such a case, the participant has not dropped out of the study, and periodic evaluation will be conducted unless the participant withdraws consent for evaluation.
(1) If the participant has never received any intervention treatment (2) When the intervention interval is more than 3 weeks.
(3) When the participant has received additional treatment for OAB at another hospital.
(4) When there are no valid data after the start of treatment.

Discontinuation of intervention
If any of the following conditions apply, the protocol treatment will be discontinued at the discretion of the physician in charge of the study.In such cases, the participant is not dropped from the study, and subsequent periodic evaluations will be conducted unless the participant withdraws consent for the evaluation.
(1) When the participant wishes to discontinue the intervention (2) When a serious AE occurs and it is deemed difficult to continue the intervention (3) When the physician in charge of the study determines that the harm of continuing the intervention outweighs the benefit for some reason, although no serious AE has occurred (4) Other cases in which the investigator deems it inappropriate to continue the intervention.

Discontinuation of valuation
If a study participant withdraws consent for a periodic evaluation, no further follow-up will be conducted.
10. Reporting of adverse events and ensuring the safety of study participants 10.1 Definition of adverse events Adverse events (AEs) are any unwanted or unintended signs or symptoms that occur in study participants, regardless of whether or not they are causally related to the intervention.For each AE, the severity, severity, transposition, and causal relationship to the intervention will be ascertained.The term "serious AE" refers to the following.If a serious AE is suspected, within 48 hours, the physician in charge will evaluate whether or not the event constitutes a serious AE, regardless of whether or not it is causally related to the drug, in accordance with the AE Reporting Protocol.If it is determined to be a serious AE, the PI will report it to the Ethics Committee of the respective institution within 72 hours.The PI will also notify all investigators, who will take necessary action based on the information provided by the PI.

Anticipated adverse events
AEs associated with CBT will not occur in the pilot study and are not anticipated.When Assuming a significance level of 5% bilaterally, a power of 80%, a symptom score difference between groups (OAB-q) of 10, and a standard deviation of 20, the sample size is 128 patients in both groups.Assuming a dropout rate of 15%, the target number of participants is 150 in both groups.

Analysis participants
As an intention-to-treat (ITT) analysis, all participants for whom allocation have been initiated will be included in the analysis.Only patients who adhere to this protocol (Per Protocol Set: PPS) will also be analyzed as a sensitivity analysis.
Definition of PPS: Participants who meet the following 4 criteria (1) Patients have received all intervention treatments.
(3) Patients have not received additional medical treatment for OAB at other hospitals (4) All measurement data are available.

Statistical analysis 11.3.1 Primary analysis
A mixed-effects model with repeated-measures (MMRM) will be used to analyze the primary outcome, the HRQoL total score of OAB-q, under the assumption of missing at random.Estimates of the least squares mean group difference, 95% confidence interval, and p-value will be calculated as the result of group × time point estimation with the change from baseline to each measurement point as the objective variable, treatment group, time point, OAB severity, interaction between treatment group and time point as fixed effects, study participants as variable effects, and baseline values as covariates.
Week 13 is the assessment point for the primary analysis.A multiple-testing procedure will be used to control for the familywise type I error rate at a two-sided significance level of 0.05.If the primary analysis at week 13 shows statistical significance, testing of other assessment points of the primary outcome is to be performed in a hierarchical manner: week 9 and week 5.

Secondary analyses
Secondary analyses will be performed to supplement the results of the primary analysis of the study and to further the discussion of the clinical question.The same statistical methods will be used for the secondary outcomes as for the primary outcome.For AEs, the number and rate of occurrence in each group will be calculated.

Subgroup analysis
The following four subgroup analyses will be performed: When possible and/or necessary,

7) Intervention type: face-to-face vs online remote session
Age is considered the most significant risk factor for OAB, and understanding of CBT may differ depending on age, as well as the effectiveness of the intervention.We believe that the severity of OAB has a strong influence on the effectiveness of the intervention.
Intervention effectiveness may differ depending on whether CBT alone or in combination with oral medication is used.Urinary incontinence is caused by weakness of the pelvic floor muscles, and the intervention effect may differ depending on the presence or absence of urinary incontinence.CBT is a psychotherapy, and treatment effects may differ in participants with anxiety or depression.Regarding the method of intervention, the treatment effect may differ between face-to-face and online.In addition, there may be different age groups among the participants who prefer face-to-face versus online.For these reasons, subgroup analyses will be conducted for age, severity, presence of urinary incontinence, and HADS scores.

Sensitivity analysis
The ITT will be used as the main analysis, and the PPS will be used as the sensitivity analysis.Furthermore, sensitivity analyses included multiple imputation approach for imputing missing data will be performed, with missing at random assumptions.
12. Study Period 12.1 Participant enrollment period Two years and 6 months from the date of approval.
12.2 Participant follow-up period Four weeks of CBT and 8 weeks of post-treatment follow-up (total 12 weeks).

Study duration
Three years from the date of approval.

Additional invasions and anticipated risks and benefits of the study
There will be a time burden associated with the completion of the self-administered symptom rating scale and the implementation of the CBT program, but no other specific risks are anticipated.No AEs were observed in the pilot study.The expected benefit is that the CBT incorporates behavioral therapy, which has originally been shown to be effective, and may lead to improvement of symptoms of OAB.

Availability of compensation for adverse health effects
Although not covered by insurance, this treatment incorporates behavioral therapy recommended in the guidelines for the treatment of OAB and is an intervention within the scope of insurance coverage.Therefore, we believe that the anticipated health hazards can also be covered by insurance.For this reason, no compensation for health damage is provided.In the event of health damage, each individual will be examined and treated by the insurance.
15. Protection of personal information 15.1 Timing and method of anonymization of samples and information All data will be entered within REDCap.After entry, the data will be anonymized with serial numbers.After anonymization, research participants will be identified by manipulating the numbers given to them.

Methods for managing the correspondence table
A new correspondence table will be created and stored at each facility.The correspondence list will be stored securely in a computer with a password.
15.3 Items of personal information to be retained or used, security control measures, and points to note Only the items obtained from the questionnaire will be used.Specifically, the following information will be used: age, height, weight, medical history, childbirth experience, menopause, last education, marital history, occupational history, treatment for voiding dysfunction, primary outcome, secondary outcomes, and AEs.As a security measure, data will be managed in REDCap, access to REDCap will be restricted to researchers, and all access will be logged in the system.Participants," we guarantee that the research participants can discontinue this research at any time if they so desire.When a research participant requests discontinuation of participation in the research, the use of such data will be discontinued.

Written explanation and consent form
The attached explanation and consent forms will be used.Access to REDCap will be restricted to researchers to prevent leakage, mix-up, theft, or loss.In addition, the system keeps a history of all accesses, which should allow for contingency measures.

Disposal after the retention period, if any
After the retention period, if consent is obtained, the correspondence list will be destroyed and uploaded to the UMIN ICDR in a form that does not identify specific individuals and stored semi-permanently.17.4 When providing and receiving information from other research institutions, create and maintain records related to the provision of such information We are considering the possibility of providing information to other research periods by uploading it to the UMIN ICDR.Since the UMIN ICDR can only be used to provide information to designated researchers, the creation and management of records will be shared.Conversely, the same will apply to the provision of information.

Cost sharing and honoraria
The intervention group will require office visits for intervention (weeks 1, 2, 3, and 4) and follow-up (weeks 5, 9, and 13); the control group will require office visits for allocation (week 1) and follow-up (weeks 5, 9, and 13).The cost of the hospital visits (re-consultation fees only) will be borne by the study participants within the insurance reimbursement.However, if the participants wish to participate in the online intervention, the consultation fee at the time of intervention will not be required.As for the gratuity, both groups will receive a gift certificate worth 1,000 yen at the week 5, 9 and 13 visits after answering each assessment item.

1. 6
Behavioral Therapy Behavioral therapy improves bladder control by helping patients change their behavior through learning urinary habits and prevention methods for urinary urgency.Specifically, it consists of lifestyle modifications, bladder training, and pelvic floor muscle training.Lifestyle modifications aim to improve aggravating factors of OAB, such as weight loss, limitation of drinking, limitation of alcohol consumption, and smoking cessation.Bladder training aims to improve symptoms by prolonging the voiding interval through making the patient hold their urine.Pelvic floor muscle training is a physical therapy program that strengthens the contractility of the pelvic floor muscles to improve symptoms.

4 .
Selection of participants 4.1.Institutions Department of Urology, Kyoto University Hospital Department of Urology, Kyoto City Hospital Department of Urology, Asukai Hospital, Kyoto Civil Medical Federation Ichioka Urology Clinic 4.2 Inclusion and exclusion criteria Inclusion criteria:

( 8 )
Participants judged otherwise unsuitable for participation by the researchers.

( 4 )
Pelvic floor muscle training Weak pelvic floor muscles are considered one of the causes of OAB.In conjunction with proper posture and breathing techniques, increase pelvic floor muscle strength through repeated awareness and contraction/relaxation exercises.

( 6 )
Relapse preventionReview the series of sessions and compare the condition before and after treatment.List the positive and negative aspects and help the participants solve problems independently, such as how to continue the treatment in the future or what to do in case of symptom exacerbation.Using these six techniques, interventions that may be effective for OAB are selected, and the therapist and the research participant collaborate to set treatment goals and assign homework for each session.Each session consists of 30 minutes and includes (1) introduction, (2) agenda, and (3) summary.The overall treatment will comprise of (1) an introduction phase (1 session), (2) a practice phase (2 sessions), and [150 -(Question Score 9+10+11+12+13+14+15+16+17+18+19+20+ 21+22+23+24+25+26+27+28+29+30+31+32+33)]/125 * 100 Secondary outcomes:

-
Change in medication (change, addition, or discontinuation) -Treatment complianceThe degree of compliance with the techniques used in each session is evaluated.of evaluation after the end of the intervention, the degree to which each technique is performed (compliance) will be assessed.

10. 2
Measures to be taken and reporting procedures in case of AEs according to the Pharmaceutical Affairs Law Since all oral treatments in this study are within the approved dosage and administration, the physician in charge will report to the MHLW if necessary, in accordance with "Article 77-4-2, Paragraph 2 of the Pharmaceutical Affairs Law" and "Kyoto University Graduate School of Medicine and Faculty of Medicine and Kyoto University Hospital Medical Ethics Committee Operating Procedures11".10.3.Measures to be taken and procedures for reporting AEs according to the Ethical Guidelines for Clinical Research In the event of a serious AE, the physician in charge will take necessary and appropriate measures to ensure the safety of the participant.According to the Ethical Guidelines for Clinical Research Q&A, what is a serious AE? A) Deadly B) Life-threatening C) Requiring hospitalization or prolonged hospitalization for treatment D) Results in permanent or significant disability or dysfunction E) Inherited birth defects.
taken concomitantly, anticholinergics or β3-adrenoceptor agonists are used.AEs associated with oral treatment include the following: Anticholinergics Main side effects: dry mouth and dry mouth, constipation, photophobia, blurred vision, dysuria, drowsiness, stomach discomfort Serious side effects: glaucoma, urinary retention, hepatic dysfunction, paralytic ileus, hallucinations/delirium, QT prolongation, ventricular tachycardia Beta 3-adrenergic receptor agonist Main side effects: constipation, dry mouth Serious side effects: urinary retention, hypertension 11.Statistical consideration 11.1 Sample size and rationale

15. 4
Persons responsible for information management of the entire research organization Principal Investigator: Takashi Kobayashi 15.5 Handling of data after withdrawal of consent Data after withdrawal of consent will not be used.Data obtained before the withdrawal of consent by the person withdrawing consent will also not be used.16.Explanation and consent 16.1 Rules and regulations to be observed In accordance with the "Declaration of Helsinki of the World Medical Association" and the "Ethical Guidelines for Life Sciences and Medical Research Involving Human

17 .
Methods for storage and disposal of samples and information 17.1 Period of storage of information Registered data will be stored at the Department of Urology, Kyoto University School of Medicine, and at each institution for 10 years after publication.17.2 Method of information storage (measures to prevent leakage, mix-up, theft, loss, etc.) Data collected at each institution will be stored in a database on REDCap, with each institution's individual participant identifiers deleted and a new research ID assigned.